Intracranial Dural Arteriovenous Fistulas with Cortical Venous Drainage: Radiosurgery as an Effective Alternative Treatment.

OBJECTIVE: To evaluate the clinical and radiological outcome of Gamma Knife radiosurgery (GKS) in treatment of intracranial dural arteriovenous fistula (DAVF) with cortical venous drainage (CVD) and compare it with the outcome of endovascular therapy. METHODS: Patients who underwent GKS or endovascular therapy for intracranial DAVF with CVD over 10 years (January 2007 to December 2016) at the All India Institute of Medical Sciences, New Delhi, were included. Demographics, clinical presentation, imaging details, and follow-up clinical status were reviewed retrospectively. Clinical follow-up was conducted once every 6 months. Radiological follow-up using digital subtraction angiography was performed at a mean 24 months after intervention. Patients with clinical follow-up of <1 year were excluded from the study. RESULTS: The study included 35 patients (26 in embolization group and 9 in GKS group) who had intracranial DAVF with CVD were included in the study. Clinical improvement was seen in 77.78% of the patients who received GKS and 57.7% of the patients who underwent embolization (P = 0.431). Complete obliteration of DAVF was seen in 55.56% of the patients in the GKS group and 57.7% of the patients in the embolization group (P = 1). GKS was at least as effective as embolization in terms of clinical and radiological outcome in treatment of intracranial DAVF with CVD. CONCLUSIONS: Contrary to popular perception, GKS should be considered as an effective first-line treatment alternative of intracranial DAVF with CVD.

Ependymosarcoma harboring C11orf95:RELA fusion transcript: Report of two cases and review of the literature.

Ependymoma is a relatively rare glial tumor of the central nervous system that arise from the cells lining the ventricles and central canal of the spinal cord. Ependymosarcoma (ES) is a newly introduced tumor entity of uncertain prognosis characterized by a rare phenomenon of a malignant mesenchymal transition arising within an ependymoma. ESs are surgically challenging tumors for diagnosis and therapy with a high incidence of morbidity and mortality. Here, we report two diagnostically challenging cases of primary ES in a 25-year-old female and a 17-year-old male. Both the cases presented with progressive and sequential neurological deficits over a period of five to eight months, and histological examination revealed a biphasic gliomesenchymal architecture comprised of anaplastic ependymomatous and sarcomatous components. Molecular genetic analysis revealed the presence of type 1 C11orf95:RELA fusion transcript. To date, 22 cases of ES have been reported in the literature, and only one case harbored type 1 C11orf95:RELA fusion transcript.

Gamma Knife Radiosurgery: The Gold Standard Treatment for Intracranial Dural Arteriovenous Fistulas without Cortical Venous Drainage.

CONTEXT: Endovascular therapy is currently the most common treatment approach for intracranial dural arteriovenous fistula (DAVF), followed by microsurgery. Gamma Knife radiosurgery (GKS) is usually reserved as the last modality of treatment of intracranial DAVF. AIM: To evaluate the clinical and radiological outcome of GKS in the treatment of DAVF without CVD. SUBJECTS AND METHODS: This series includes patients who underwent GKS for intracranial DAVF without CVD over 10 years (Jan 2007 to Dec 2016) in All India Institute of Medical Sciences, New Delhi. Their demographic profile, clinical presentation, imaging details, GKS details, and follow-up clinical status were obtained retrospectively. Clinical follow-up, along with radiological assessment using MRI every 6 months was done after GKS. DSA was performed once MRI strongly suggested obliteration of DAVF. Patients who had a clinical follow-up of less than 1 year were excluded from the study. RESULTS: 5 patients (4 males and 1 female) who had DAVF without CVD were included the study. The mean age was 44.8 years. All patients had complete obliteration of fistula on digital subtraction angiography (DSA) at a mean duration of 24 months post GKS. All patients had complete resolution of symptoms at the last follow-up. CONCLUSIONS: Gamma Knife surgery is the most effective and the safest treatment modality for dealing with DAVFs without CVD. Instead of reserving it as the last resort for patients with DAVF without CVD, it should be considered as the gold standard treatment for DAVFs without CVD.

Transcriptional regulation of HSPB1 by Friend leukemia integration-1 factor modulates radiation and temozolomide resistance in glioblastoma.

Glioblastoma (GBM) is the most common primary brain tumor and is invariably fatal. Heat shock proteins (HSPs) provide protein signatures/biomarkers for GBM that afford potential as targets for developing anti-GBM drugs. In GBM, elevated expression of hypoxia inducible factors under the influence of Ets family proteins significantly promotes the expression of HSPs. RNAseq analysis identified HSPB1 as a prominent upregulated HSP in GBM and in radiation resistant/temozolomide resistant (radio/TMZR) GBM. Here, we established friend leukemia integration 1 (Fli-1), a member of Ets family to be playing a transcriptional regulatory role on the HSPB1 gene. Fli-1 binds to nucleotide residues GGAA at binding sites 3, 6 and 7 in the 5-kb upstream region of HSPB1. Fli-1 has been linked to oncogenic transformation with upregulation in radio/TMZR GBM. Overexpression of Fli-1 in GBM promotes resistance, whereas Fli-1 knockdown in radio/TMZR GBM cells suppresses resistance. We identify the underlying molecular mechanisms of Fli-1-mediated regulation of HSPB1 that drive extracellular matrix remodeling and epithelial to mesenchymal transition in radio/TMZR GBM cells. This study uncovers Fli-1 as a potential therapeutic target for combating radiation and temozolomide resistance in GBM.

Primary intracranial malignant ectomesenchymoma in an adult: Report of a rare case and review of the literature.

Malignant ectomesenchymoma (MEM) is an exceedingly rare rapidly progressing tumor of soft tissues of the central nervous system, believed to be derived from neural crest cells. The majority of cases have been observed in young children or adolescents. So far only 11 patients with intracranial manifestations (with confirmed clinicopathological data) have been documented. We report the first case of adult intracranial MEM in a 54-year-old man who presented with a 4 months history of headache and weakness of right side of the body. Magnetic resonance imaging showed a homogenously enhanced dural-based lesion in the left fronto-temporo-parietal lobe with significant perilesional edema and mass effect. No metastatic disease was identified and the lesion was grossly resected. Histopathological and immunohistochemical examination revealed mature and immature neurons and bizarre astrocytes admixed with a mesenchymal spindle cell (rhabdomyoblastic) component. Specific risk factors that contribute toward the development of MEM are unknown. Due to the scarcity of reported cases the role of adjuvant therapy is unclear.

Economic and social impact of out-of-pocket expenditure on households of patients attending public hospitals.

BACKGROUND: We aimed to generate evidence on the social and economic impact of out-of-pocket expenses incurred by households on illness. METHODS: We did a hospital-based cross-sectional study including a convenience sample of 374 inpatients and outpatients. RESULTS: The median illness expenditure was the same (₹62 500) for inpatients and outpatients. Of all respondents, 51.3% among the rural and 65.5% among the urban patients were employed before illness, but after illness only 24.4% among the rural and 23.4% among the urban patients remained in employment. The proportion of rural households of different socioeconomic categories that experienced decrease in expenditure on food, education and health, and those who had to sell land or cattle, and the education of whose children suffered was statistically significant. The proportion of indebted families in different socioeconomic classes was also statistically significant among both rural and urban patients. The lowest socioeconomic strata depended mostly upon the financial support of their friends to tide over the financial crisis of an illness. CONCLUSION: Our study shows that out-of-pocket expenses on healthcare are a burden not only for the poor but also the middle classes.

Errors of inclusion and exclusion in income-based provisioning of public healthcare: Problems associated with below poverty line cards.

This study examined the effect of out-of-pocket expenditure of patients on their illness and other household changes impacting on their well-being, and assessed the socioeconomic status and below poverty line (BPL) card status among patients at the All India Institute of Medical Sciences, New Delhi. We did a hospital-based cross-sectional study of 374 inpatients and outpatients. Among the 374 study subjects, more than 69% of poor did not possess a BPL card. On the other hand, 5.5% of the above poverty line patients among the respondents possessed a BPL card. Of those having BPL cards, 84.4% belonged either to the lower middle, upper lower and lower socioeconomic status categories. Our data suggest that the inaccuracies in providing BPL cards limit access of the genuine poor to healthcare. In the light of national-level surveys on accessing healthcare and out-of-pocket expenditure by patients there is a case against 'targeting' in the delivery of public health services and user charges have an adverse impact on access to healthcare by the poor.

A rare case of white pearls in brainstem.

Intrinsic brainstem epidermoid is extremely rare, and only 14 cases have been reported. Authors report a classic case of brainstem epidermoid in a 14-year-old male child presenting with symptoms of brainstem involvement. The child underwent a successful surgical excision. The lesion was intrinsic and caused diagnostic dilemma based on conventional radiological images. Based on our experience in this case and a thorough review of literature, we are of the opinion that diffusion-weighted images are very important in establishing the diagnosis. Such lesions are challenging and attempt to remove adherent tumor capsule may produce additional neurological deficits.

Pediatric interhemispheric arachnoid cyst: An institutional experience.

BACKGROUND: Interhemispheric arachnoid cysts (IHACs) are a rare type of congenital arachnoid cyst accounting for <5% of all cases. The optimum surgical management of symptomatic IHAC is still controversial, and there are no clear guidelines. MATERIALS AND METHODS: Retrospective analysis of six pediatric patients of IHAC operated from 2012 to 2015 at our institute. There was definitive sex predisposition with all patients being males. Endoscopic cystoventriculostomy, cystocisternostomy, and cystoperitoneal shunt surgeries were performed in three patients each. RESULTS: The median age at presentation was 13 months. The most common clinical presentations were macrocrania with rapidly increasing head size, seizures, infantile spasms, and developmental delay. The mean duration of follow-up was 24.16 months (range: 3-36 months). Cyst size decreased in all the patients on follow-up imaging. Head size stabilized in all the patients. None of the patients required a second surgical procedure till the last follow-up. CONCLUSIONS: Both endoscopic cyst fenestration and shunt surgery are safe and effective in management of IHAC.

Extracellular matrix protein lumican regulates inflammation in a mouse model of colitis.

BACKGROUND: Abnormal innate immune response contributes to inflammatory bowel disease (IBD) and experimental mouse colitis. Colitis studies have focused primarily on key regulators of innate immunity, like pathogen recognition receptors and cytoplasmic mediators. Extracellular matrix (ECM) proteins are emerging as modulators of inflammatory responses by virtue of their interactions with pathogen-associated molecular patterns (PAMPs), cytokines, growth factors, receptors, and ECM fragments that mimic pathogens or cytokines. The ECM proteins have not been investigated in IBD at great depth from this standpoint. We have shown previously that the ECM protein lumican modulates host sensing of bacterial lipopolysaccharides (LPS) by Toll-like receptor (TLR) 4, and neutrophil chemotaxis via integrins. METHODS: Here we investigated the role of lumican in the development of colitis mediated by intrarectal administration of the hapten 2-4-5, trinitrobenzene sulfonic acid (TNBS) in Lum(+/+) and Lum(-/-) mice. RESULTS: The TNBS treated Lum(+/+) mouse colons showed marked increases in CXCL1, tumor necrosis factor alpha (TNF-α), and neutrophil infiltration, whereas these responses were significantly dampened in the Lum(-/-) mice. The nuclear factor kappa B (NF-κB) transcription factor, known to regulate inflammatory genes, showed a robust increase after TNBS treatment in Lum(+/+) but not in Lum(-/-) colons. Also, nuclear translocation of NF-κB was delayed in LPS stimulated Lum(-/-) primary peritoneal macrophages. CONCLUSIONS: The Lum(-/-) mice have low innate immune and inflammatory responses, but more severe body weight loss and tissue damage, a phenomenon seen in the innate immune impaired Tlr4(-/-) and MyD88(-/-) mice. Therefore, lumican promotes intestinal homeostasis by aiding innate immune and inflammatory responses that are beneficial in the early stages of colitis.